Suppressor T cells are a population of lymphocytes produced by the thymus and whose function is to suppress immune responses. They are particularly important in the induction of immunological tolerance and in the breakdown of normal tolerance to auto-antigens, a situation that can lead to an "auto-immune" type of disease process. Suppressor T cells appear to play a role in auto-immune diseases involving the pituitary, ovary and thyroid gland. Although the pathogenesis of many cases of diabetes suggests that an auto-immune process might be involved, the role of suppressor T cells in pancreatic disease does not appear to have been investigated. The proposed research is designed to test the hypothesis that suppressor T cells have a role in the development of at least some cases of diabetes. The spontaneous development of abnormalities of pancreatic function, determined by glucose tolerance tests, plasma and pancreatic insulin levels, and morphology at the light and electron microscopic levels will be determined in rats which have either been neonatally thymectomized (reducing both helper and suppressor T cell numbers) or perinatally thymectomized (preferentially reducing suppressor T cell numbers). The effect on the occurrence of pancreatic abnormalities in thymectomized rats, of active immunization with homogenate of whole pancreas or with individual islets or of repeated exposure to doses of sub-lethal irradiation (4x150 rads) which selectively depresses suppressor T cell numbers, will be determined. Cell substitution experiments involving the transfer of thymus, spleen and lymph node cells from normal donors to thymectomized recipients treated in such a way as to render them susceptible to pancreatic disease will be performed. Using this technique, cell populations effective at preventing induced pancreatic disease will be defined. Such populations will be partially characterized as to their suppressor T cell content by measurement of their differential mitogenic response to stimulation by phytohemagglutinin and concanavalin A.